Microcystin-LR

IC50: 1.7 nM and 0.04 nM for type 1 and type 2A protein phosphatases, respectivley.

Protein phosphatases 1 and 2A, two of the major phosphatases in eukaryotic cells that dephosphorylate serine and threonine residues. Microcystin-LR is a potent inhibitor of type 1 and type 2A protein phosphatases.

In vitro: Microcystin-LR inhibited protein phosphatases 1 (PP1) and 2A (PP2A) with Ki values below 0.1 nM. Protein phosphatase 2B is inhibited 1000-fold less potently, while six other phosphatases and eight protein kinases tested are unaffected. Microcystin-LR inhibited enzymes in a remarkably similar manner to okadaic acid, a potent tumour promoter that is also the toxin responsible for diarrhetic shellfish poisoning [1].

In vivo: After 100 i.p. injections of a sublethal dose (20 μg/kg) of MCLR, neoplastic nodules were observed without the use of an initiator. Multiple neoplastic nodules up to 5 mm in diameter were observed in the liver of mice in both groups, i.e. those injected 100 times i.p. and those injected 100 times with a 2 month withdrawal. In contrast, when 80 μg/kg was orally administered 100 times, characteristic chronic injuries such as fibrous changes and nodule formation were not observed [2].

Clinical trials: Currenlty no clinical data are available.

References:
[1] MacKintosh C, Beattie KA, Klumpp S, Cohen P, Codd GA.  Cyanobacterial microcystin-LR is a potent and specific inhibitor of protein phosphatases 1 and 2A from both mammals and higher plants. FEBS Lett. 1990 May 21;264(2):187-92.
[2] Ito E, Kondo F, Terao K, Harada K.   Neoplastic nodular formation in mouse liver induced by repeated intraperitoneal injections of microcystin-LR. Toxicon. 1997 Sep;35(9):1453-7.